TumorMicroenvironmentDynamicsinClearCellRenalCellCarcinomaLyndaVuong^,1,2,RiteshR.Kotecha^,3,MartinH.Voss3,A.AriHakimi4,11Immunogenomics&PrecisionOncologyPlatform,MemorialSloanKetteringCancerCenter,NewYork,NY2HumanOncologyandPathogenesisProgram,MemorialSloanKetteringCancerCenter,NewYork,NY3DepartmentofMedicine,MemorialSloanKetteringCancerCenter,NewYork,NY4DepartmentofUrology,MemorialSloanKetteringCancerCenter,NewYork,NYAbstractRenalcellcarcinomastandsoutasoneofthemostimmuneinfiltratedtumorsinpan-cancercomparisons.Featuresofthetumormicroenvironmentheavilyimpactdiseasebiologyandmayaffectresponsestosystemictherapy.Withevolvingfrontlineoptionsinthemetastaticsetting,severalimmunecheckpointblockaderegimenshaveemergedasefficacious,andthereisgrowinginterestincharacterizingfeaturesoftumorbiologythatcanreproduciblyprognosticatepatientsand/orpredictthelikelihoodofderivingtherapeuticbenefit.Herein,wereviewpertinentcharacteristicsofthetumormicroenvironmentwithdedicatedattentiontocandidateprognosticandpredictivesignaturesaswellaspossibletargetsforfuturedrugdevelopment.IntroductionRenalcellcarcinoma(RCC)isthemostcommonformofkidneycancerclaimingover14,000livesperyearintheUnitedStates1.Clinically,onethirdofpatientswillpresentwithmetastaticRCC(mRCC)2.Coupledwithrelapsingmetastasesinaquarterofpatientswith“local”diseasefollowingcurativenephrectomy,mRCCconstitutesasubstantialmedicalburden2.AlthoughallRCCsarisefromthenephronsandreceivesimilarclinicalregimens,histologicalsubtypesarehighlyheterogenousintheirbiologyandtherapeuticoutcomes3.Themostcommon(70–80%)subtype,clearcellRCC(ccRCC)isalsooneofthemostaggressive3.Generallyinsensitivetocytotoxicchemotherapyanduniquelydependentontumorangiogenesis,ccRCCemergedearlyastheprototypesolidtumormalignancyforapplicationofmolecularlytargetedagents,particularlytyrosinekinaseinhibitors(TKIs)targetingthevascularendothelialgrowthfactorreceptor(VEGFR)pathway2.Secondly,ccRCChaslongCorrespondingAuthor:A.AriHakimi;DepartmentofUrology,MemorialSloanKette...
